Age-dependent regulation of glucocorticoid receptors in the liver of male rats

Abstract

Specific binding of [ 3H]dexamethasone to cytosol and the activation of bound hormone-receptor complexes were studied in the liver of immature (3 weeks old) and mature (26 weeks old) Long-Evans male rats. The concentration of specific binding sites was significantly higher (33%) in the liver of immature rats as compared to mature, while dissociation constants ( K d) remain unaltered at both ages. Heat activation (for 45 min at 25° C) significantly enhances the binding of [ 3H]dexamethasone-receptor complexes to DNA-cellulose and purified nuclei at both the ages, with a greater magnitude in mature rats. Cross mixing experiments (i.e., binding of activated cytosol from mature rats to nuclei of immature and vice-versa) show receptor specificity. Ca 2+ activation (20 mM Ca 2+ for 45 min at 0° C) also enhances the nuclear and DNA-cellulose binding at both the ages, but to a similar extent. Differences in the number of specific binding sites and some of the physicochemical properties of glucocorticoid receptors presented here between immature and mature rats may underlie the functional changes in tissue response with age.